Structural Insights into the Methane-Generating Enzyme from a Methoxydotrophic Methanogen Reveal a Restrained Gallery of Post-Translational Modifications

• Main Authors: Julia Maria Kurth, Marie-Caroline Müller, Cornelia Ulrike Welte, Tristan Wagner
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Microorganisms
• Subjects: methyl-coenzyme M reductase; post-translational modifications; methoxydotrophic methanogenesis; X-ray crystallography; F₄₃₀-cofactor; thermophilic archaeon
• Online Access: https://www.mdpi.com/2076-2607/9/4/837

Methanogenic archaea operate an ancient, if not primordial, metabolic pathway that releases methane as an end-product. This last step is orchestrated by the methyl-coenzyme M reductase (MCR), which uses a nickel-containing F₄₃₀-cofactor as the catalyst. MCR astounds the scientific world by its unique reaction chemistry, its numerous post-translational modifications, and its importance in biotechnology not only for production but also for capturing the greenhouse gas methane. In this report, we investigated MCR natively isolated from <i>Methermicoccus shengliensis</i>. This methanogen was isolated from a high-temperature oil reservoir and has recently been shown to convert lignin and coal derivatives into methane through a process called methoxydotrophic methanogenesis. A methoxydotrophic culture was obtained by growing <i>M. shengliensis</i> with 3,4,5-trimethoxybenzoate as the main carbon and energy source. Under these conditions, MCR represents more than 12% of the total protein content. The native MCR structure refined at a resolution of 1.6-Å precisely depicts the organization of a dimer of heterotrimers. Despite subtle surface remodeling and complete conservation of its active site with other homologues, MCR from the thermophile <i>M. shengliensis</i> contains the most limited number of post-translational modifications reported so far, questioning their physiological relevance in other relatives.